title: Anti-apoptotic and neuroprotective effects of oxysophoridine on cerebral ischemia both in vivo and in vitro.
abstract: In this study, we investigated the neuroprotective effect of oxysophoridine on ischemia and ischemia-like insults. Protection by oxysophoridine was studied at the in vivo level using a model of middle cerebral artery occlusion in mice and at the in vitro level using primary rat hippocampal neuronal cultures exposed to oxygen-glucose deprivation, a model of ischemia-like injury. The behavioral test was performed by using the neurological scores. The infarction volume of brain was assessed in the brain slices stained with 2,3,5-triphenyl tetrazolium chloride. The neuron apoptosis was evaluated by Hoechst 33342 staining. The morphological change in the neurons was examined using a Transmission Electron Microscope (TEM or EM). To evaluate neuron apoptosis, caspase-3, -9, and - 8 activities were measured using assay kits with an ELISA reader. The Western blotting assay was used to evaluate the release of cytochrome c and expression of caspase-3, Bcl-2, and Bax proteins. The quantitative real-time PCR assay was used to evaluate the release of cytochrome c and the expression of caspase-3 mRNA. Oxysophoridine-treated groups (62.5, 125, 250 mg/kg) markedly reduced neurological deficit scores and infarct volumes. Treatment with oxysophoridine (5, 20, 80 µmol/L) significantly attenuated neuronal damage, with evidence of decreased cell apoptosis and decreased cell morphologic impairment. Furthermore, treatment with oxysophoridine could effectively downregulate the expression of cytochrome c and caspase-3 in both mRNA and protein levels, and Bax in the protein level, and induce an increase of Bcl-2 in the protein level. The caspase-3, -9, and -8 activities were also inhibited. These findings suggested that oxysophoridine may be a potential neuroprotective agent for cerebral ischemia injury.
authors.affiliation: Department of Pharmacology, Ningxia Medical University, Yinchuan, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Rui
authors.forename: Li
authors.initials: L
authors.lastname: Yuxiang
authors.forename: Jiang
authors.initials: J
authors.lastname: Ning
authors.forename: Ma
authors.initials: M
authors.lastname: Ningtian
authors.forename: Zhu
authors.initials: Z
authors.lastname: Qingluan
authors.forename: Hao
authors.initials: H
authors.lastname: Yinju
authors.forename: Zhou
authors.initials: Z
authors.lastname: Ru
authors.forename: Ma
authors.initials: M
authors.lastname: Lin
authors.forename: Sun
authors.initials: S
authors.lastname: Tao
authors.forename: Yu
authors.initials: Y
authors.lastname: Jianqiang
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000470:Alkaloids; D018696:Neuroprotective Agents; D051028:bcl-2-Associated X Protein; C406983:oxysophoridine; D045304:Cytochromes c; D053148:Caspase 3